公开(公告)号：US20030105357A1

公开(公告)日：2003-06-05

申请号：US10209427

申请日：2002-07-30

Applicant: Yeda Research And Development Co. Ltd.

Inventor： Yehuda Mazur ,  Gad Lavie

IPC: C07C239/00

CPC classification number: A61K31/136 ,  A61K31/122 ,  A61K31/235

Abstract: Hypericin, helianthrone and derivatives thereof of general formula (I) 1 wherein the dotted line between positions 11 and 12 represent an optional C11-C12 bond; R is independently selected from the group consisting of hydroxy, C1-C10 alkoxy, NHnullC1-C10 alkyl, and NH-hydroxy(C1-C10)alkyl; Rnull is independently selected from the group consisting of hydroxy and C1-C10 alkoxy; Rnull is independently selected from the group consisting of hydrogen, hydroxy, C1-C10 alkoxy, NHnullC1-C10 alkyl, and NH-hydroxy(C1-C10)alkyl; and R1, R2, R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, hydroxy, chloro, bromo, C1-C10 alkyl, C1-C10 alkoxy, and C1-C10 alkoxycarbonyl, provided that Rnull is not hydrogen when there is a C11-C12 bond, are useful as inhibitors of angiogenesis and can be used to prevent formation of metastases and restenosis and for the treatment of angiogenesis-associated ophthalmologic disorders. In addition, the helianthrones of formula (I) can be used for the treatment of tumors in the absence of light irradiation. New compounds include those of formula I which are other than hypericin and known hypericin derivatives and there is either a C11-C12 bond or at least one Rnull is other than hydrogen.

Abstract translation: 通式（I）的金丝桃素，向日葵及其衍生物，其中位置11和12之间的虚线表示任选的C 11 -C 12键; R独立地选自羟基，C 1 -C 10烷氧基，NH-C 1 -C 10烷基和NH-羟基（C 1 -C 10）烷基; R'独立地选自羟基和C 1 -C 10烷氧基; R“独立地选自氢，羟基，C 1 -C 10烷氧基，NH-C 1 -C 10烷基和NH-羟基（C 1 -C 10）烷基; R 1，R 2，R 3，R 4，R 5和R 6独立地选自氢，羟基，氯，溴，C 1 -C 10烷基，C 1 -C 10烷氧基和C 1 -C 10烷氧基羰基，条件是R“ 当存在C11-C12键时，不是氢，可用作血管发生的抑制剂，可用于预防转移和再狭窄的形成以及用于治疗血管发生相关的眼科疾病。 此外，式（I）的长方体可用于在不存在光照射的情况下治疗肿瘤。 新化合物包括除金丝桃素和已知金丝桃素衍生物之外的式I的那些，并且存在C 11 -C 12键或至少一个R“不是氢。